Genome-wide search for a candidate gene in systemic lupus erythematosus

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790991
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: The University of Tokushima
• Principal Investigator: KITAMURA Akiko The University of Tokushima, 大学院・ヘルスバイオサイエンス研究部, 助教 (10448318)
• Project Period (FY): 2009 – 2010
• Keywords: 全身性エリテマトーデス / ポジショナルクローニング

Research Abstract

Systemic lupus erythematosus (SLE) is a multifactorial disease in which both genetic and environmental factors are involved. Genome wide association studies revealed many predisposing genes to common forms of SLE. However, those studies have failed to identify genes that strongly contribute to the pathogenesis of SLE. We found one consanguineous SLE family, which consists of 3 affected and 1 unaffected sibling. To identify the underlying gene, we performed a homozygosity mapping and revealed two homozygous regions (FSLE-1, FSLE-2) that spanned 0.7 Mb and 1.1 Mb, respectively. MLOD score was 1.7 and 2.5, respectively. The FSLE-1 did not contain any gene, but the FSLE-2 region contained 40 known and predicted genes. We plan to perform the capture-resequencing analysis of the FSLE-2 region.

Research Products

• [Journal Article] Notch signaling regulates the development of a novel type of Thy1-expressing dendritic cell in the thymus. (2011)
  • Author(s): Ishifune C, Maekawa Y, Nishida J, Kitamura A, Tanigaki K, Yagita H, Yasutomo K.
  • Journal Title: Eur J Immunol 41 Pages: 1309-1320
• [Journal Article] Notch signaling drives IL-22 secretion in CD4+ T cells by stimulating the aryl hydrocarbon receptor. (2010)
  • Author(s): Alam MS, Maekawa Y, Kitamura A, Tanigaki K, Yoshimoto T, Kishihara K, Yasutomo K.
  • Journal Title: Proc Natl Acad Sci USA 107 Pages: 5943-5948
• [Journal Article] ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis. (2010)
  • Author(s): Urushihara M, Takamatsu M, Shimizu M, Kondo S, Kinoshita Y, Suga K, Kitamura A, Matsuura S, Yoshizumi M, Tamaki T, Kawachi H, Kagami S.
  • Journal Title: Am J Physiol Renal Physiol 298 Pages: F167-F176
• [Journal Article] Notch2 signaling is required for potent anti-tumor immunity in vivo. (2010)
  • Author(s): Sugimoto K, Maekawa Y, Kitamura A, Nishida J, Koyanagi A, Yagita H, Kojima H, Chiba S, Shimada M, Yasutomo K.
  • Journal Title: J Immunol 184 Pages: 4673-4678
• [Journal Article] Jagged1 suppresses collagen-induced arthritis by indirectly providing a negative signal in CD8+ T cells. (2009)
  • Author(s): Kijima M, Iwata A, Maekawa Y, Uehara H, Izumi K, Kitamura A, Yagita H, Chiba S, Shiota H, Yasutomo K.
  • Journal Title: J Immunol 182 Pages: 3566-3572
• [Journal Article] Predisposition to relapsing nephrotic syndrome by a nephrin mutation that interferes with assembly of functioning microdomains. (2009)
  • Author(s): Shono A, Tsukaguchi H, Kitamura A, Hiramoto R, Qin XS, Doi T, Iijima K.
  • Journal Title: Hum Mol Genet 18 Pages: 2943-2956
• [Presentation] Identification of a candidate locus in familial systemic lupus erythematosus by homozygosity mapping (2009)
  • Author(s): Akiko Kitamura, Koji Yasutomo
  • Organizer: American Society of Human Genetics 2009 Annual Meeting
  • Place of Presentation: Hawaii Convention Center (USA)
  • Year and Date: 2009-10-21
• [Presentation] ホモ接合体マッピングによる家族性全身性エリテマトーデスの疾患遺伝子探索 (2009)
  • Author(s): 北村明子、安友康二
  • Organizer: 第54回日本人類遺伝学会
  • Place of Presentation: グランドプリンスホテル高輪(東京)
  • Year and Date: 2009-09-26